MiR-21 is Involved in Transforming Growth Factor β1-induced Chemoresistance and Invasion by Targeting PTEN in Breast Cancer

Overview

Journal Oncol Lett

Specialty Oncology

Date 2017 Nov 21

PMID 29151919

Citations 22

Authors

Xiaomeng Dai

Mao Fang

Shuang Li

Yongrong Yan

Ying Zhong

Bin Du

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor β1 (TGF-β1) has been associated with poor outcomes in patients with breast cancer. However, the functions and underlying molecular mechanisms of TGF-β1 in breast cancer remain unknown. Therefore, the present study aimed to identify the effects of components of the TGF-β/microRNA (miR-)21/phosphatase and tensin homolog (PTEN) signaling axis in breast cancer. TGF-β1 was identified to upregulate the expression of miR-21, and miR-21 was demonstrated to be significantly upregulated in breast cancer tissues compared with benign proliferative breast disease. In addition, the expression of miR-21 was significantly associated with increased TGF-β1 and clinical characteristics in patients, including tumor grade and lymph node metastasis (all P<0.05). Furthermore, in the breast cancer MCF-7 cell line, TGF-β1 was revealed to induce the expression of miR-21 in a dose- and time-dependent manner. The results of the present study additionally demonstrated that increased miR-21, in response to TGF-β1 signaling, was associated with tumor invasion and chemoresistance . In addition, suppression of PTEN was mediated by TGF-β1-induced expression of miR-21 in breast cancer cells and using a miR-21 inhibitor revitalized the expression of PTEN. The results of the present study explored the functions of TGF-β1-stimulated expression of miR-21 to suppress the PTEN axis, which promotes breast cancer progression and chemoresistance.

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References

Wieser R . The transforming growth factor-beta signaling pathway in tumorigenesis. Curr Opin Oncol. 2001; 13(1):70-7. DOI: 10.1097/00001622-200101000-00014. View

Xiao X, Liao X, Qiu S, Liu Z, Du B, Xu S . Synthesis, cytotoxicity and apoptosis induction in human tumor cells by galaxamide and its analogues [corrected]. Mar Drugs. 2014; 12(8):4521-38. PMC: 4145329. DOI: 10.3390/md12084521. View

Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M . Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006; 9(3):189-98. DOI: 10.1016/j.ccr.2006.01.025. View

Imamura T, Hikita A, Inoue Y . The roles of TGF-β signaling in carcinogenesis and breast cancer metastasis. Breast Cancer. 2011; 19(2):118-24. DOI: 10.1007/s12282-011-0321-2. View

Zhang H, Wu H, Zheng J, Yu P, Xu L, Jiang P . Transforming growth factor β1 signal is crucial for dedifferentiation of cancer cells to cancer stem cells in osteosarcoma. Stem Cells. 2012; 31(3):433-46. DOI: 10.1002/stem.1298. View

Noetel A, Kwiecinski M, Elfimova N, Huang J, Odenthal M . microRNA are Central Players in Anti- and Profibrotic Gene Regulation during Liver Fibrosis. Front Physiol. 2012; 3:49. PMC: 3307137. DOI: 10.3389/fphys.2012.00049. View

Wu Z, Tao Z, Zhang J, Li T, Ni C, Xie J . MiRNA-21 induces epithelial to mesenchymal transition and gemcitabine resistance via the PTEN/AKT pathway in breast cancer. Tumour Biol. 2015; 37(6):7245-54. DOI: 10.1007/s13277-015-4604-7. View

Padua D, Massague J . Roles of TGFbeta in metastasis. Cell Res. 2008; 19(1):89-102. DOI: 10.1038/cr.2008.316. View

Katsuno Y, Hanyu A, Kanda H, Ishikawa Y, Akiyama F, Iwase T . Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene. 2008; 27(49):6322-33. DOI: 10.1038/onc.2008.232. View

10.

Santa-Maria C, Gradishar W . Changing Treatment Paradigms in Metastatic Breast Cancer: Lessons Learned. JAMA Oncol. 2015; 1(4):528-34. DOI: 10.1001/jamaoncol.2015.1198. View

11.

Stambolic V, Macpherson D, Sas D, Lin Y, Snow B, Jang Y . Regulation of PTEN transcription by p53. Mol Cell. 2001; 8(2):317-25. DOI: 10.1016/s1097-2765(01)00323-9. View

12.

Davis B, Hilyard A, Lagna G, Hata A . SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008; 454(7200):56-61. PMC: 2653422. DOI: 10.1038/nature07086. View

13.

Kitamura K, Seike M, Okano T, Matsuda K, Miyanaga A, Mizutani H . MiR-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther. 2013; 13(2):444-53. DOI: 10.1158/1535-7163.MCT-13-0448. View

14.

Dey N, Ghosh-Choudhury N, Kasinath B, Ghosh Choudhury G . TGFβ-stimulated microRNA-21 utilizes PTEN to orchestrate AKT/mTORC1 signaling for mesangial cell hypertrophy and matrix expansion. PLoS One. 2012; 7(8):e42316. PMC: 3411779. DOI: 10.1371/journal.pone.0042316. View

15.

Chung A, Dong Y, Yang W, Zhong X, Li R, Lan H . Smad7 suppresses renal fibrosis via altering expression of TGF-β/Smad3-regulated microRNAs. Mol Ther. 2012; 21(2):388-98. PMC: 3594008. DOI: 10.1038/mt.2012.251. View

16.

Silberstein G, DANIEL C . Reversible inhibition of mammary gland growth by transforming growth factor-beta. Science. 1987; 237(4812):291-3. DOI: 10.1126/science.3474783. View

17.

Ghoncheh M, Pournamdar Z, Salehiniya H . Incidence and Mortality and Epidemiology of Breast Cancer in the World. Asian Pac J Cancer Prev. 2016; 17(S3):43-6. DOI: 10.7314/apjcp.2016.17.s3.43. View

18.

Giunti L, Da Ros M, Vinci S, Gelmini S, Iorio A, Buccoliero A . Anti-miR21 oligonucleotide enhances chemosensitivity of T98G cell line to doxorubicin by inducing apoptosis. Am J Cancer Res. 2015; 5(1):231-42. PMC: 4300700. View

19.

Muraoka R, Dumont N, Ritter C, Dugger T, Brantley D, Chen J . Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest. 2002; 109(12):1551-9. PMC: 151012. DOI: 10.1172/JCI15234. View

20.

Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S . PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997; 275(5308):1943-7. DOI: 10.1126/science.275.5308.1943. View